Summary

Objective. Cholangiocarcinoma (CCA) is an aggressive malignancy with limited therapeutic options and poor prognosis. Advances in next-generation sequencing (NGS) revealed distinct molecular profiles between intrahepatic (iCCA) and extrahepatic (eCCA) subtypes, identifying recurrent mutations with diagnostic and therapeutic significance. We evaluated the performance of a laboratory-developed NGS panel designed for the integrated diagnostic and predictive profiling of CCA.

Methods and Results. In this multicentric retrospective study, 50 biopsies were analyzed, achieving 92% success rate. Pathogenic variants were identified in 58.7% of samples, with TP53 (26.1%) and KRAS (21.7%) as the most frequently mutated genes. Multiple mutations were observed in 14 cases, the most frequent co-mutation being KRAS plus TP53 (6 cases). Non-druggable but diagnostically relevant genes (e.g., ARID1A, BAP1) were added  to enhance classification accuracy.

Conclusions. Despite limitations such as inability to detect gene fusions (e.g., FGFR2), the panel demonstrated strong analytical feasibility and clinical utility. Integrating DNA/RNA sequencing, optimized pre-analytical workflows, and multidisciplinary interpretation will refine precision oncology approaches for CCA management in the future.

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Authors

Dario de Biase - Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

Thais Maloberti - Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

Giulia Ciccimarra - Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

Laura Poppi - Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

Deborah Malvi - Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Michele Carroli - Pathology Unit, Santa Maria delle Croci Ravenna Hospital, Ravenna, Italy.

Luca Saragoni - Pathology Unit, Santa Maria delle Croci Ravenna Hospital, Ravenna, Italy. Department of Medical and Surgical Sciences (DIMEC), University of Bologna.

Giovanni Tallini - Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

Francesco Vasuri - Pathology Unit, Santa Maria delle Croci Hospital, Ravenna, Italy.

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Copyright

Copyright (c) 2026 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
de Biase, D., Maloberti, T., Ciccimarra, G., Poppi, L., Malvi, D., Carroli, M., Saragoni, L., Tallini, G., & Vasuri, F. (2026). Custom Next-Generation Sequencing panel for cholangiocarcinoma diagnostic profiling. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 118(3). Retrieved from https://www.pathologica.it/article/view/1790
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